Cocaine dependence continues to be a major social and medical problem nationwide. Moreover, cocaine abuse is a substantial problem among women, with women making up approximately 30% of cocaine abusers seeking treatment. Women become dependent on cocaine more rapidly than men do, and female drug users are more likely than male drug users to be in treatment for "hard" drugs of abuse, such as cocaine and heroin. The majority (73%) of all cocaine treatment admissions are for smoked cocaine and 42% of individuals admitted for smoking crack cocaine were women. This increase in crack cocaine use, particularly among women, has indirectly been associated with an increase in sexually transmitted HIV. Despite this, no concerted efforts have been made to target a pharmacological treatment for female cocaine abusers. Our recent laboratory studies in non-treatment seeking cocaine abusers have shown that oral micronized progesterone reduces the positive subjective effects of cocaine administration and these effects are more robust in females than in males. Further, oral micronized progesterone actually attenuates cocaine-induced increases in cardiovascular effects indicating that this medication may be protective against cocaine toxicity. Lastly, preliminary data indicate that oral micronized progesterone decreases smoked cocaine self- administration in females. Oral micronized progesterone, as opposed to synthetic progestins, has a high safety profile and can be administered to women for prolonged periods, with the most common side effects being sedation and irregular menstrual bleeding. Taken together, these findings suggest that oral micronized progesterone may have clinical utility in reducing cocaine use in cocaine-dependent women seeking treatment. The objective of this RFA is to support pilot clinical trials of medications for substance abuse, including special populations. As such, we propose to conduct a randomized placebo-controlled treatment trial to evaluate the efficacy of oral micronized progesterone compared to placebo in women dependent on crack cocaine. One of the biggest problems in pharmacological treatment trials with substance abusers is poor compliance and retention. We will use voucher incentives for clinic attendance to enhance retention and we will provide brief compliance enhancement therapy. The results of this pilot treatment trial will provide a preliminary basis on which to decide whether to undertake a large-scale clinical trial that would include a more heterogeneous group of women (i.e., women who primarily use cocaine by other routes other than smoked). [unreadable] [unreadable] [unreadable]